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Electron micrograph of 2019 n-CoV.

January 31, 2020- 

I awoke this morning to an onslaught of scary new “Coronavirus” headlines. Just yesterday, the World Health Organization (WHO) declared the 2019 novel coronavirus (2019-nCoV) a “global public health emergency,” a designation reserved for serious and/or sudden diseases that may threaten public health internationally and which could “potentially require a coordinated international response.”  

Scary headline from NBS news. Image source here.

This emergency designation was motivated by the need to prevent the spread of the virus into countries with less developed healthcare systems, which could result in uncontrollable spread. Briefly, 2019-nCoV is a virus that causes a pneumonia-like illness in infected people, has a two-week incubation period, and has been shown to be able to be transmitted between people. See “Resources” for some great starting material to learn more.

Taking a look at how quickly scientists, public health officials, academic institutions, construction workers, and government agencies around the world have responded to this new threat always gives me hope, and I aim to share that with you. Below are the amazing strides made in research thus far: 

The “China Novel Coronavirus Investigating and Research Team” identify and describe features of 2019-nCoV: based on publication in New England Journal of Medicine (24 Jan 2020) 

Fluid from the airways of three patients was collected, and whole genome sequencing (where the complete DNA of an organism is determined) identified the novel virus in all three patients. 2019-nCoV genome sequences were made publically available, and the 25 available sequences -as of today- can be downloaded from GenBank here.

Zhu et. al then used virus obtained from these fluid samples to inoculate human airway cell cultures and examine the effects. Light microscopy revealed that compared to mock-infected cells (A), virus-infected human airway cells (B) do not appear to be beating their cilia, tiny hairs that typically serve as a defense mechanism for the airways by moving mucus up and out.

We are looking at cilia (grainy little dots) covering the surface of a layer of human cells that normally line the airway. We see that the cilia looks to be more uniform on the left, while there is a loss of pattern on the right, which we infer to mean that the cilia on the right are not beating as they should.

Chinese CDC scientists release genomic characterizations of 2019-nCoV: based on publication in the Lancet (30 Jan 2020)

In this paper, complete genome sequences of 2019-nCoV were obtained from eight patients and (1) compared against each other, (2) compared to reference genomes that were closest in sequence identity (bat SARS-like betacoronavirus, bat SLCoVZC45 and bat-SL-CoVZXC21, and (3) to the genome of SARS-CoV. 

(1) Sequence identity between 2019-nCoV genomes and significance 

Each one of the codes on the left is a 2019-nCoV genome sequence obtained from one patient, and each red vertical line represents a single nucleotide difference. As we can see, there are very few differences from one patient to another.

The eight complete 2019-nCoV genomes obtained from patients showed  98-99% sequence similarity, which suggest that the virus only recently showed up in humans (the virus hasn’t had enough time to acquire mutations). 

(2,3) Comparison of the 2019-nCoV sequence to other bat-SARS-like-CoV sequences and SARS-CoV 

Visual representation of the likeness of 2019-nCoV (green) genome compared to SARS-CoV (red) compared to Bat-SARS-like-CoV (blue, purple). 1.00 on the y axis represents 100% similarity, while the x-axis represents location in the genome.

From the above graph, it is clear that the 2019-nCoV genome sequence more closely resembles the bat-SARS-like-CoV sequences than SARS-CoV, with the most notable deviations from all 3 in the region encoding the spike protein “S”. This data indicates that bats are natural hosts for 2019-nCoV, though the authors note that the <90% sequence identity between 2019-nCoV and bat-SARS-like-CoV likely implicates a more recent ancestor and therefore an intermediate host for the virus. In simpler terms, it means viral transmission likely moved from bat → unknown animal → human.

The coronavirus spike proteins  “S” consist of two subunits – a variable S1 subunit, responsible for recognition of and binding to host cell receptors, and a highly conserved S2 subunit, which is responsible for fusion of the viral particle to the host cell. In short, spike proteins are how viruses establish themselves in human host cells. Importantly, Roujian Lu et al. found that the 2019-nCoV protein sequence of “S” looked more like SARS-CoV “S” than the bat-SARS-like-CoV “S”, which points to a potential common method of the two viruses’ ability to bind and invade human cells. 

Structure of a Coronavirus. The spike proteins coat the virus.

The researchers then modeled the binding region in S1 of three human viruses SARS-CoV, 2019-nCoV, and MERS-CoV. Note how the bottom half of 2019-nCoV, which is the part of the virus that purportedly interacts with human cells, looks a LOT like the bottom half of SARS-CoV. This means that maybe, 2019-nCoV binds to the same human host cell receptor that SARS-CoV does! 

Striking similarity between the parts of 2019-nCoV and SARS-CoV that contact the human host cells.

Wuhan scientists shed light on how 2019-nCoV is able to enter human cells: based on bioRxiv preprint by Peng Zhou et al (23 Jan 2020)

SARS-CoV binds to a receptor called ACE2. Figure 4 in this paper (which I cannot show here because it is a preprint, but please go see the real thing) showed that the 2019-nCoV could only invade and replicate cells that were making ACE2 but not in cells that were not making ACE2. This demonstrates that 2019-nCoV can invade human cells making ACE2, but whether this mechanism of entry actually happens in people infected with 2019-nCoV remains to be determined. 

Graphic describing the experiment done in the paper. Image source here.

Australian scientists at the Doherty Institute successfully grow 2019-nCoV in Culture (29 Jan 2020)

Researchers at the Doherty Institute in Melbourne released a video of 2019-nCoV growing in culture. In this short video, visualized through what appears to be inverted phase contrast light microscopy, infected cells (dark) divide again and again. What seems like a phagocytic cell in the upper left corner eats as many infected cells as it can, but is hopelessly outpaced by the relentless rate of viral infection.

Johns Hopkins University generates a map tracking the geographical distribution in real-time (22 Jan 2020)

JHU Center for Systems Science and Engineering released a map showing confirmed 2019-ncoV cases worldwide in real-time, putting the outbreak into perspective with information and statistics from WHO, the Centers for Disease Control and Prevention (CDC), European Centre for Disease Prevention and Control, Chinese CDC, and the National Health Commission of the People’s Republic of China. Importantly, the data used to generate the map can also be downloaded and could serve as a valuable source for epidemiological research.

Such swift strides in research were enabled by massively coordinated efforts and rapid outbreak response of the Chinese government as well as other governments around the world, and I deeply respect and appreciate all those working to contain the spread of this virus.

In hope, 
the microbepipettor
*please feel free to comment if something should be corrected. 

Resources
If you are unfamiliar with what nCoV is, I recommend these starting materials:
(1) (24 Jan 2020)  2:28 minute video from Nature video- with great graphics!, https://www.youtube.com/watch?v=Q_4fIkc2k6g 
(2) (updated 30 Jan 2020) CDC summary, if you prefer reading https://www.cdc.gov/coronavirus/2019-ncov/summary.html

Sources in order of reference:
[1] https://www.nbcnews.com/health/health-news/new-coronavirus-outbreak-declared-global-public-health-emergency-who-says-n1126836
[2] https://www.nejm.org/doi/full/10.1056/NEJMoa2001017?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed
[3] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30251-8/fulltext
[4] https://www.biorxiv.org/content/10.1101/2020.01.22.914952v1.full.pdf

microbepipettor